Racemization behavior of l,l-lactide during heating

To control the depolymerization process of poly(l-lactic acid) into l,l-lactide for feedstock recycling, the racemization of l,l-lactide as a post-depolymerization reaction was investigated. In the absence of a catalyst, the conversion to meso-lactide increased with increase in the heating temperature and time at a higher rate than the conversion into oligomers. The resulting high composition of meso-lactide suggests that the direct racemization of l,l-lactide had occurred in addition to the known racemization mechanism that occurs on the oligomer chains. In the presence of MgO, the oligomerization rapidly proceeded to reach an equilibrium state between monomers and oligomers. The equilibrium among l,l-, meso-, and d,d-lactides was found to be a convergent composition ratio l,l-:meso-:d,d-lactides = 1:1.22:0.99 (wt/wt/wt) after 120 min at 300 °C. This composition ratio also indicates that in addition to the known racemization reaction on the oligomer chains, direct racemization among the lactides is also a frequent occurrence.     

New pyrano[3,4-b]indoles from 2-hydroxymethylindole and l-dehydroascorbic acid

2-Hydroxymethylindole reacts with l-dehydroascorbic acid under mild conditions to give (3R,3aR,10cS)-3-[(1S)-1,2-dihydroxyethyl]-3a,10c-dihydroxy-3a,5,6,10c-tetrahydrofuro[3′,4′:5,6]pyrano[3,4-b]indol-1(3H)-one. Its tosyl derivative undergoes cyclization to form a pentacyclic ketal derivative.     

One-pot inversion of d-mannono-1,4-lactone for the practical synthesis of l-ribose

l-Ribose was synthesized in a concise manner from d-mannono-1,4-lactone using one-pot inversion conditions. Treatment of d-mannono-1,4-lactone with piperidine, followed by mesylation-induced S_N2-type O-alkylation, afforded the desired one-pot inversion in an optimum yield, and the following straightforward transformations provided l-ribose in good yields.     

A highly efficient synthesis of unnatural l-sugars from d-ribose

A preparative and short synthesis of l-ribose and l-apiose was accomplished starting from d-ribose via stereoselective cis-dihydroxylation and C2-hydroxymethylation, respectively. These l-sugars can serve as versatile intermediates for the synthesis of l-nucleosides.     

A d,l-proline catalyzed diastereoselective trimolecular condensation: an approach to the one-pot synthesis of perhydrofuro[3,2-b]pyran-5-ones

d,l-Proline was found to catalyze efficiently the one-pot trimolecular condensation of indoles, a sugar hydroxyaldehyde, and Meldrum’s acid followed by intramolecular cyclization with evolution of carbon dioxide and elimination of acetone to afford 7-(1H-3-indolyl)-2,3-dimethoxyperhydrofuro[3,2-b]pyran-5-ones. The reaction proceeded cleanly at ambient temperature to afford the products in good yields with high diastereoselectivity.     

A general approach to l-tyrosine porphyrins

A novel and general approach has been developed to prepare l-tyrosine-containing porphyrins. The key intermediates, 2-tert-butoxycarbonylamino-3-(3-formyl-4-hexyloxy-phenyl)-propionic acid hexyl ester and 2-tert-butoxycarbonylamino-3-(3-formyl-4-methoxy-phenyl)-propionic acid methyl ester, were prepared by the Reimer-Tiemann reaction of Boc-protected l-tyrosine, which was followed by esterification and alkylation of the phenol hydroxide. A number of novel chiral l-tyrosine porphyrins were obtained from the reactions of 2-tert-butoxycarbonylamino-3-(3-formyl-4-alkoxy-phenyl)-propionic acid ester with different dipyrrolylmethanes and the reaction of 5-(4-trifluoromethylphenyl)pyrromethane afforded the highest yield. The tyrosine porphyrins could be readily deprotected to afford the corresponding diacid or diamine derivatives.     

An efficient synthesis of d-ribo-C18-phytosphingosine and l-arabino-C18-phytosphingosine from d-fructose

d-ribo-C₁₈-phytosphingosine and l-arabino-C₁₈-phytosphingosine were synthesised starting from commercially inexpensive d-fructose. Metal-mediated fragmentation and stereoselective reduction were used as key steps to provide the hydrophilic portion of d-ribo and l-arabino phytosphingosines. Grubbs’ cross-metathesis and hydrogenation allowed the incorporation of hydrophobic tail.     

Intermolecular/interionic interactions in l-isoleucine-, l-proline-, and l-glutamine-aqueous electrolyte systems

Speed of sound and density values for ternary systems (amino acid + salt + water): l-isoleucine/l-proline/l-glutamine in aqueous solutions of 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ have been measured for several concentrations of amino acids at different temperatures (303.15, 308.15, 313.15, 318.15, and 323.15 K). Using speed of sound and density data, the thermodynamic parameters such as isentropic compressibility (κ_s), change in isentropic compressibility (Δκ_s) and relative change (Δκ_s/κ₀) in isentropic compressibility have been computed. The isentropic compressibility values decrease with increase in the amino acid concentration as well as with temperature. The decrease in κ_s values with increase in concentration of l-isoleucine/l-proline/l-glutamine in 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ has been ascribed to an increase in the number of incompressible zwitterions in solutions, and the formation of ‘zwitterions-ions’ and ‘zwitterions-water dipole’ entities in solutions. The decrease in κ_s values with increase in temperature has been attributed to the corresponding decrease of κ_relax (a relaxational part of compressibility), which is dominant over the corresponding increase of κ_∞ (an instantaneous part of compressibility). The trends of variation of Δκ_s and Δκ_s/κ₀ with variations in solute concentration and temperature have also been discussed in terms of solute-solute and solute-solvent intermolecular/interionic interactions operative in the systems.     

Novel synthesis of 5-thio-hexopyranoside: preparation of 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose

Asymmetric synthesis of both d- and l-isomers of 5-thioglucose and 1,6-anhydro-5-thioaltrose are described. The key intermediates, l- and d-threose diethylacetal derivatives, were derived by chemical transformation from d-xylose or d-arabinose and by Sharpless asymmetric dihydroxylation from γ-hydroxycrotylaldehyde diethylacetal. They transformed to γ-thiiranyl diethylacetal via trans-2,3-epoxy alcohol in seven steps. Acetic acid-promoted cyclization of γ-thiiranyl diethylacetal gave 5-thiopyranoside. Removal of the protected groups under the acidic conditions afforded 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose, respectively.     

Effects of molecular weight and small amounts of d-lactide units on hydrolytic degradation of poly(l-lactic acid)s

Films of poly(l-lactic acid) (PLLA) with different number-average molecular weights (M_n) and d-lactide unit contents (X_d) were made amorphous and the effects of molecular weight and small amounts of d-lactide units on the hydrolytic degradation behavior in phosphate-buffered solution at 37 °C of PLLA were investigated. The degraded films were investigated using gravimetry, gel permeation chromatography, polarimetry, differential scanning calorimetry, X-ray diffractometry, and tensile testing. To exclude the effects of crystallinity on the hydrolytic degradation, the films were made amorphous by melt-quenching. The incorporation of small amounts of d-lactide units drastically enhanced the hydrolytic degradation of PLLA. In the period of 0-32 weeks, the hydrolytic degradation rate constant (k) of PLLA films increased with increasing X_d, while the k values did not depend on M_n. This means that the effects of X_d on the hydrolytic degradation rate of the films are higher than those of M_n. In contrast, in the period of 32-60 weeks neither X_d nor M_n was a crucial parameter to determine k values, probably because in addition to these parameters the differences in the amount of catalytic oligomers accumulated in films and crystallinity affect the hydrolytic degradation behavior of the films. The initially amorphous PLLA films remained amorphous even after the hydrolytic degradation for 60 weeks.     

Selection of synthetic receptors capable of sensing the difference in binding of d-Ala-d-Ala or d-Ala-d-Lac ligands by screening of a combinatorial CTV-based library

Screening of a combinatorial CTV-based artificial, synthetic receptor library 1 {1-13, 1-13, 1-13} for binding of a variety d-Ala-d-Ala and d-Ala-d-Lac containing ligands (6-11) was carried out in phosphate buffer (0.1 N, pH=7.0). After screening and Edman sequencing, synthetic receptors were found containing amino acid sequences, which are either characteristic for binding dye labeled d-Ala-d-Ala or d-Ala-d-Lac containing ligands. For example, receptors capable of binding d-Ala-d-Ala containing ligands 6, 7, 9 and 11 contained—almost in all cases—at least one basic amino acid residue—predominantly Lys—in their arms. This was really a striking difference with the arms of the receptors capable of binding d-Ala-d-Lac containing ligands 8 and 10, which usually contained a significant number of polar amino acids (Gln and Ser), especially in ligand 8, but hardly any basic amino acids. Use of different (fluorescent) dye labels showed that the label has a profound, albeit not decisive, influence on the binding by the receptor. A hit from the screening of the CTV-library with FITC-peptidoglycan (6) was selected for resynthesis and validation.     

Kinetics of thermo-oxidative and thermal degradation of poly(d,l-lactide) (PDLLA) at processing temperature

Poly(d,l-lactide) (PDLLA) degraded at processing temperature under air and nitrogen. A random chain scission model was established and used to determine the activation energy E_a, and FT-IR, ¹H and ¹³C NMR were used to elucidate the degradation behavior under different atmospheres. Results showed that there were two to three stages. The 1st stage was dominated by the oligomers containing carboxylic acid groups and hydroxyl groups, during which oxygen and nitrogen had little effect on the degradation, thus they share similar E_a. When the oligomers were consumed over or evaporated, the 2nd stage began, and oxygen had a promoting effect on the thermo-oxidation process, resulting in the great decrease in E_a. The third stage of PDLLA was observed when it degraded under nitrogen over 200 °C, which was caused by the appearance of carboxylic acid substance.     

Stereoselective synthesis of the phytotoxic nonenolide herbarumin-I from l-ascorbic acid

A stereoselective synthesis of herbarumin-I in 22% overall yield, starting from l-ascorbic acid derived (S)-2,3-O-isopropylidine glyceraldehyde as a chiral template is reported. Stereoselective allylation and vinylation to control the required stereogenic centres and macrolactonisation followed by a ring-closing metathesis (RCM) are the key steps.     

A new efficient and practical synthesis of 2-deoxy-l-ribose

An efficient and practical route for large-scale synthesis of 2-deoxy-l-ribose starting from l-ascorbic acid was developed in eight steps without chromatographic purification for all intermediates. Additionally, (2S,3R)-3,4-epoxy-1,2-O-isopropylidenebutane-1,2-diol, a versatile intermediate in carbohydrate synthesis, was also prepared readily in excellent yield as a key intermediate.     

Efficient synthesis of new N-alkyl-d-ribono-1,5-lactams from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 9a in quantitative yield. Bromination of amide 9a by the system SOBr₂ in DMF or PPh₃/CBr₄ in pyridine led, after acetylation, to epoxide 7. However, treatment of amide 9a with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxyl-N-ethyl-d-ribonamide 10a. Methanolysis of 10a, with sodium methoxide, afforded the N-ethyl-d-ribonolactam 11a in 51% overall yields. Using this method, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonolactams 11b-e were obtained in good yields (48-53%).     

Prevailing mechanisms of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans

The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans in phosphate buffer was followed by quantifying both released dextran and lactic acid from the copolymers. The studied amphiphilic copolymers, with well-defined structure, exhibited various oligo(d,l-lactide) weight fractions (F^OLA) while having a quite high extent of free hydroxyl groups (>90%). Depending on their F^OLA, oligo(d,l-lactide)-grafted dextrans were soluble either in water or in organic solvents (THF, toluene, …) and different prevailing mechanisms of hydrolytic degradation were observed. The copolymer soluble in THF, with longer oligo(d,l-lactide) grafts and higher F^OLA, was found to degrade via a particular mechanism by which the greatest part of dextran was released into buffer medium during the first two weeks of degradation. During the initial stage of degradation, the hydrophilicity of dextran backbone was considered to be the main driving force for the hydrolytic cleavage of the ester linkage between backbone and grafts. Released oligo(d,l-lactide) grafts were found to be degraded via chain-end degradation or random degradation depending on their solubility in buffer medium. In case of water-soluble copolymers with shorter oligo(d,l-lactide) grafts and lower F^OLA, the chain-end degradation was exclusively observed.     

Intermolecular/interionic interactions in l-leucine-, l-asparagine-, and glycylglycine-aqueous electrolyte systems

Ultrasonic velocity and density values have been measured for ternary systems (amino acid/di-peptide + salt + water): l-leucine/l-asparagine/glycylglycine each in 1.5 M aqueous solutions of NaCl or NaNO₃ or KNO₃ used as solvents for several concentrations of amino acids/di-peptide at different temperatures in the range of 298.15-323.15 K. The ultrasonic velocity values have been found to increase with increase in amino acids/di-peptide concentration and temperature in all the systems. The increase in ultrasonic velocity with increase in concentration has been discussed in terms of electrostatic interactions occurring between terminal groups of zwitterions (NH₄⁺ and COO⁻) and Na⁺, K⁺, Cl⁻, NO₃⁻ ions. The interactions of water dipoles with cations/anions and with zwitterions have also been taken into consideration. It has been observed that the ion-zwitterion and ion-dipole attractive forces are stronger than those of ion-hydrophobic repulsive forces. These interactions comprehensively introduce the cohesion into solutions under investigation. The cohesive forces are further enhanced on successive increases in solute concentration. Using ultrasonic velocity and density data, the parameters such as isentropic compressibility (κ_s), change (Δκ_s) and relative change (Δκ_s/κ₀) in isentropic compressibility, specific acoustic impedance (Z) and relative association (RA) have been computed. The isentropic compressibility values decrease with increase in the concentration of solutes as well as with temperature. The decrease in κ_s values with increase in concentration of l-leucine, l-asparagine and glycylglycine in 1.5 M aqueous solutions of NaCl, NaNO₃ and KNO₃ have been explained in terms of an increase in the number of incompressible molecules/zwitterions in solutions and the formation of compact zwitterions-water dipole and zwitterions-ions structures in solutions. The decrease in κ_s values with increase in temperature has been attributed to the corresponding decrease of κ_relax. (relaxational part of compressibility)_, which is dominant over the corresponding increase of κ_∞ (instantaneous part of compressibility). The trends of variations of Δκ_s, Δκ_s/κ₀, Z and RA with change of concentration and temperature have also been interpreted in terms of various intermolecular/interionic interactions existing in the systems.     

A convenient synthesis of l-ribose from d-fructose

An efficient method for the stereoselective synthesis of l-ribose was accomplished starting from commercially inexpensive d-fructose. The intermediates in the process can serve as versatile precursors for the preparation of l-nucleoside analogues.     

Amperometric simultaneous sensing system for d-glucose and l-lactate based on enzyme-modified bilayer electrodes

An amperometric biosensor system which uses screen-printed electrodes to simultaneously detect d-glucose and l-lactate has been developed and applied for simple and rapid determination of d-glucose and l-lactate levels in lactic fermenting beverages. The system was constructed from three-dimensionally layered electrodes. Taking into consideration the effects of easily oxidized substances contained in the samples, ferricyanide ions, which are electrochemically oxidized at a lower voltage, were chosen as a mediator. A linear relationship between steady-state current and concentration was found over a range of 1-100 mM (d-glucose) and 1-50 mM (l-lactate); the variation coefficients were 1.43% (n = 10) and 3.50% (n = 10) for the d-glucose and l-lactate sensors, respectively. When applied to lactic fermenting beverages, there was good agreement between the results obtained by the proposed sensing system and those obtained by the HPLC method. Using the proposed method, assays were completed within 5 min.